At any time, nearly half of the 500,000 people in the United States living with multiple sclerosis (MS), a common and disabling neuro-inflammatory disease of the central nervous system, have a progressive course. Despite the explosion of new MS therapies, there remains a frustrating lack of disease-modifying therapies that can alter the functional decline of progressive MS (PMS) that resulting in reduced community participation, low quality of life, and high burdens on health care systems and caretakers. Lipoic acid (LA) is an inexpensive, endogenously-produced, oral antioxidant with multiple biological functions implicated in the pathogenesis of PMS. LA reduces disability in a dose- dependent fashion in the animal model of MS, and is safe and tolerated in people with MS. A 2- year randomized, double-blind, placebo-controlled clinical trial of daily oral LA in secondary progressive MS, a subset of PMS patients, demonstrated a remarkable 68% reduction in the annualized rate of whole brain atrophy, the current gold-standard MRI biomarker in PMS. While not powered to do so, the LA cohort exhibited a trend toward improvement in walking tests and a reduction in falls. This study proposes to expand on the highly promising preliminary results to confirm the effects of LA on reducing rates of brain atrophy and to determine its associated clinical benefits. The design is a multi-center, double-blind, randomized, placebo-controlled trial of oral daily LA in a PMS population with the following objectives: 1. Determine if LA is superior to placebo in maintaining a clinically meaningful outcome, mobility, as measured by the primary outcome of change in completion time of the Timed 25 Foot Walk as suggested by the pilot study. Falls and other walking tests will be evaluated to confirm the primary outcome results. 2. Determine if LA is superior to placebo in slowing whole brain atrophy with an estimated 40-50%% effect size. This will confirm our previous findings of a significant 68% reduction in brain atrophy rate at a more modest effect size that is in line with protection of brain atrophy rates from relapsing MS trials. Additional secondary outcome measures will include neurological disability, cognition, mood, and quality of life. 3. Monitor safety and tolerability via laboratory testing and adverse event reporting. Participants at 3 or 4 sites with PMS will be randomized on a 1:1 basis to LA or placebo. Participants will be enrolled over 18 months and complete 7 study visits over 2 years. Walking tests will be performed at every visit. MRIs will be completed at baseline and study end. Secondary endpoints not related to MRI will be collected at study visits every 6 months. Safety labs will be collected at every study visit and adverse events every 3 months. The sample size of 50 per arm will allow for a 15% drop-out rate. The Portland VA Medical Center will be the lead coordinating site. Monthly conference calls and biannual site visits will assure uniformity and high quality of study data. A web-based database, centralized MRI reading center, and experienced data analysis center will be utilized. The results of this study, once confirmed, will set the stage for large-scale phase 3 clinical trials of LA for the treatment of PMS, filling a much needed gap in MS therapeutics, and resulting in improved health, safety, and quality of life for Veterans with MS.